ReviewPain and depression comorbidity: A preclinical perspective

•Pain and depression co-exist and exacerbate one another both in clinical and preclinical findings.•Pain and depression seem to have a reciprocal causative relationship.•Domain interplay concept may foster future development of new pain-depression comorbidity models.

Pain and depression are two highly prevalent and deleterious disorders with significant socioeconomic impact to society. Clinical observations have long recognized the co-existence and interactions of pain and depression. However, the underlying mechanisms of pain-depression comorbidity and their dynamic interactions remain largely unknown. Preclinical animal studies may provide critical information for the understanding of this important comorbidity. This review analyzed the current preclinical evidence of interactions between pain and depression, which generally supports the causative relationship of the two conditions. In addition, the analysis proposed to apply domain interplay concept in future model development of pain-depression comorbidity and mechanism studies. The application of spectrum-centered animal models will better the understanding of pain-depression dyad and foster the development of more effective therapeutic strategies.